The dorsal cochlear nucleus (DCN) is the first neural site of bimodal auditory-somatosensory integration. Previous studies have shown that
Given the well described connection between the somatosensory system and tinnitus in patients we sought to determine whether
in vivo long-term effects of somatosensory inputs on acoustically evoked discharges of DCN neurons in guinea pigs. The effects of
trigeminal nucleus stimulation are compared between normal-hearing animals and animals overexposed with narrow band noise and
behaviorally tested for tinnitus. The noise exposure resulted in a temporary threshold shift in auditory brainstem responses but a
persistent increase in spontaneous and sound-evoked DCN unit firing rates and increased steepness of rate-level functions. Rate in-
creases were especially prominent in buildup units. The long-term somatosensory enhancement of sound-evoked responses was
cochlear nucleus (DCN) receives somatosensory inputs from
head, neck, upper body and limbs via the trigeminal and dorsal
column systems, which are transmitted by parallel fibers to syn-
Arvidsson, 1988; Shore et al., 2000; Zhou and Shore, 2004;
Haenggeli et al., 2005; Zhan et al., 2006). In normal-hearing an-
imals, paired somatosensory and auditory stimulation leads to
suppression or enhancement of acoustically evoked discharges
with suppression dominating (Shore, 2005; Shore et al., 2007;
Kanold et al., 2011; Koehler et al., 2011). While those studies
described the immediate effects of trigeminal and dorsal column
stimulation, long-term effects have not been studied in vivo in
either normal or noise-damaged systems.
be an important factor in tinnitus development. Auditory nerve
damage leads to enhancements of somatosensory inputs and their
physiological effects in the DCN (Shore et al., 2008; Zeng et al.,
2009). Increased glutamatergic somatosensory innervation and in-
creased sensitivity to those inputs after noise damage might be an
underlying mechanism for tinnitus development, with tinni-
tus being a pathological auditory response to enhanced tonic so-
matosensory inputs. The connection between tinnitus and the
somatosensory system is supported by (1) the observation that tin-
al., 2002; Biesinger et al., 2008), (2) patients can develop tinnitus
after somatosensory insults such as tooth abscess, whiplash, and
Here we studied immediate and long-term effects of so-
matosensory modulation of sound-evoked discharges in DCN
neurons in vivo in control and noise-exposed guinea pigs.
Results of a behavioral tinnitus test (Turner et al., 2006) were
correlated with changes in somatosensory modulation. A
comparison between animals with and without tinnitus was
made to reveal changes in auditory-somatosensory processing
analysis and Ben Yates for excellent graphic assistance. We thank Jeremy Turner for valuable discussions and
yngology and Molecular and Integrative Physiology, University of Michigan, 1150 W. Medical Center Drive, Ann
1660 • TheJournalofNeuroscience,February1,2012 • 32(5):1660–1671
as a neuronal correlate and possible underlying cause for tin-
Noise exposure resulted in a temporary threshold shift (TTS)
in spontaneous and sound-evoked DCN unit firing rates and
in buildup units of tinnitus animals. After paired somatosensory-
(the longest interval tested). In the noise-exposed animals somato-
hancement. Chopper as well as buildup units in tinnitus animals
showed a strong dominance of long-term enhancement over sup-
development, in which increased excitatory somatosensory influ-
Animals. Male pigmented guinea pigs from Cady Ridge Farms (300 g at
study onset) were used in this study. All procedures were performed in
accordance with the National Institutes of Health Guidelines for the Use
of the University of Michigan. Of the 20 animals used for DCN record-
were tested behaviorally for tinnitus (7 noise-exposed and 4 sham-
exposed control animals). The numbers of animals contributing to each
analysis are indicated in the figure legends.
Gap-detection testing for tinnitus. The gap detection test for tinnitus
response elicited by loud pulses and its suppression by preceding sub-
startling prepulses, here gaps in noise bands. It is assumed that ongoing
gap detection testing was performed using a Kinder Behavioral Testing
System. Testing chambers were placed within a single-walled sound-
proofed booth. Oscillograms of the gap-in-background noise bands
and their spectra were examined for reverberations, harmonics and
frequency-specificity. The signal spectra outside the gap-carrier/noise
pulse bands were between 19 dB SPL and 24 dB SPL for each of the
frequency bands of the gap-carrier/noise pulses (4–6 kHz, 19 dB SPL;
8–10 kHz and 12–14 kHz, 23 dB SPL; 16–18 kHz, 24 dB SPL). Gap-
phone (Bru ¨el and Kjaer1⁄4 inch 4136), spectrum analyzer (SR760,
cage. A 15 ms gap (excluding 5 ms offset/onset ramps) was embedded in
at 70 dB SPL. The startle pulse (115 dB SPL, BBN, 20 ms) followed the
presentation) was varied pseudo randomly (from 0 to 5 s) to prevent
anticipation of the startle and interval-based habituation. Detection of
the gap results in a reduction in the startle amplitude; development of
tinnitus in a specific frequency band impairs gap detection in the corre-
tudes elicited without the gap (Turner et al., 2006). Animals with
normalized startle values (i.e., startle with gap/startle without gap) close
to 1 after the noise exposure were grouped together as animals with
tinnitus (normalized startles for 8–10 kHz: 0.98 up to 1.46 compared
exposed control group. In addition to the gap detection test, animals
were also tested with a noise pulse-prepulse inhibition (PPI) test, in
the gap; with the same timing as the gap and the same frequency-
composition as the gap carrier (see Fig. 4B). Normal noise pulse detec-
tion validates that hearing loss is not the cause for diminished gap-PPI
twice a week and continued for the time between the two noise
Noise exposure. The noise exposure was performed under anesthesia (14
mg/kg body weight xylazine, AnaSed Injection, Akorn Inc.; and 110 mg/kg
ketamine, Hospira Inc.; additional dose 4 mg/kg xylazine and 13 mg/kg
ketamine). Body temperature was kept constant using a temperature-
controlled heating pad. The left ear was exposed for 2 h while the right ear
was plugged with moldable silicon ear plugs. After the recovery of ABR
was inserted 2 mm tightly into the ear canal. The noise was generated with
to a Bru ¨el and Kjaer1⁄4 inch microphone (4136) and spectrum analyzer
(SR760, Stanford Research Systems). The noise (see Fig. 3) had a 7 kHz
muscularly with an antibacterial solution to prevent infections (enro-
injected with 10 ml of saline and treated with antibacterial eardrops
(ofloxacin, 0.3%, Floxin Otic, Daiichi Sankyo Inc.).
ABRs were collected using BioSigRP software and RX5/RA4LI hard-
ware (Tucker-Davis Technologies). The speaker (Beyer DT 48) calibra-
tion and acoustic stimulation were performed with SigGenRP software
and RX8/PA5 hardware (Tucker-Davis Technologies). The speaker was
coupled to the animals’ ear canal via a 2 cm plastic tube inserted into the
noise exposure (left and right ears). ABRs after the exposures were per-
formed weekly on days following the behavioral testing (Tuesdays or
Dehmeletal.•SomatosensoryTinnitus J.Neurosci.,February1,2012 • 32(5):1660–1671 • 1661
40 mg/kg body weight ketamine). Body temperature was kept constant
with a temperature controlled heating pad. Sanded 0.6 mm * 25 mm
seter muscles were used for recording, grounding and reference elec-
frequencies 4–16 kHz) starting at 90 dB SPL and decremented in 10 dB
steps. Each level was repeated 250 times and the lower levels around
threshold were rerun to record a second set of 250 presentations. ABR
waveforms were visually inspected across levels; threshold was the lowest
level of sound that resulted in one or more of the ABR waves being distin-
Extracellular multiunit recordings. DCN recordings were performed
10–21 d (average 16 d) after the second noise exposure. Animals were
anesthetized with ketamine (40 mg/kg) and xylazine (10 mg/kg) and
and partial aspiration of the cerebellum overlying the DCN was per-
formed to allow visual placement of the probes (4 shank/16 channel
?m below the DCN surface. Stimulation and multiunit recordings were
achieved using OpenEx software (Tucker-Davis Technologies), which
controlled RX8 DSP and RX5 respectively. Thresholds and center fre-
quencies (CFs) were determined online (OpenExplorer, Tucker-Davis
ms duration tone (200 ms stimulation period) at each frequency-level
dB SPL). RLFs were generated for 50 repetitions of each 5 dB step. To
assess immediate effects of bimodal stimulation, a tone RLF (a series of
tone burst stimuli between 0 and 85 dB) was immediately followed by a
bimodal RLF (electric Sp5 stimulation preceding each tone stimulus by
RLF and then tone RLFs were subsequently repeated for up to 135 min
min; Fig. 2). In some animals, RLFs were recorded before and after Sp5
stimulation alone to obtain control data (data not shown) that indicated
that the long-term effect was due to paired stimulation and not Sp5
stimulation alone. Poststimulus time histogram type was determined
from the tone RLFs 20–40 dB above threshold and then averaged across
units of all animals and within the groups of control, tinnitus and no-
The caudal and intermediate regions of Sp5 were electrically stimu-
lated with a custom-made isolated high-voltage current source via con-
centric bipolar electrodes (FHC) placed stereotaxically (Koehler et al.,
2011). The electrical stimulus at 60 ?A preceded the tone stimulus by 20
ms and consisted of 2 biphasic square pulses, 100 ?s per phase, with the
to create lesions and to transport the Fluoro Gold into the tissue. The
animals were killed and decapitated, and the head was fixed in parafor-
maldehyde for 4 d. The brain was removed from the skull, fixed over-
night, immersed in sucrose solution and then cryosectioned (100 ?m
Gold marks observed with light and fluorescent microscopy.
1662 • J.Neurosci.,February1,2012 • 32(5):1660–1671 Dehmeletal.•SomatosensoryTinnitus
nologies). K-means clustering with a fixed variance (95%) and maxi-
excluded if the shape and size of each cluster and average waveform
across the recordings were not consistent. Responses were analyzed for
the time window of the tone presentation.
ter the current pulses were not included in this
To quantify the immediate and long-term ef-
ences across tone levels were calculated A) (1)
between a tone RLF and an immediately subse-
quent bimodal RLF (“immediate” effect of bi-
RLF and a second tone RLF on average 35 min
after the bimodal stimulation (“long-term”).
Data points (number of units * sound levels of
RLFs) were grouped into rate-enhancement
(white graphs; first tone response ? bimodal re-
sponse (1) or first tone response ? later tone re-
sponse (2)) and rate-suppression (black graphs;
first tone response ? bimodal response (1) or
first tone response ? later tone response (2)).
pie charts showing the number of data points
change summed across units and all sound lev-
els). Arrows and stars in the rate difference plots
indicate the results of linear mixed model statis-
tics comparing all observed rate differences of a
group (either immediate or long-term effects of
ject with two difference-RLFs (immediate and
data for within immediate rate differences or
each unit, repeated factor is “sound level of the
term rate differences of control animals’ data,
noise-exposed animals’ data, tinnitus animals’
cept for each unit, repeated factor is “immediate
and long-term” and “sound level of the RLF.”
Pairwise comparison of immediate versus
long-term or control versus exposed, tinni-
tus or no-tinnitus was done across all sound
levels (significances labeled with stars), ad-
justment for multiple comparisons: Sidak,
critical level p ? 0.05.
Data analysis, statistics and plotting were
performed with OpenExplorer (Tucker-Davis
Technologies), SPSS (Version 17), and Sigma-
Plot (Version 11.0, Systat Software Inc.).
Overexposure with a narrow band noise
centered at 7 kHz resulted in an immedi-
ate ABR threshold shift between 6 and 16
kHz with a maximum of 50 dB mean
threshold shift at 8 kHz (Fig. 3; mean of
individual animal’s ABR differences be-
fore versus immediately after the exposure; nondirectional one-
sample t test against a mean threshold shift of 0 dB for each test
frequency, df ? 9, minimum p ? 0.001, maximum p ? 0.002).
and 95% confidence intervals are shown as dotted horizontal lines below and above the mean. The mean ? 95% confidence
Dehmeletal.•SomatosensoryTinnitus J.Neurosci.,February1,2012 • 32(5):1660–1671 • 1663
Four of the seven animals developed tin-
nitus for frequencies between 8 and 18
kHz by the time of recovery of ABR
4). The normalized startles of these “tin-
nitus” animals were increased toward or
above one; and were maximal in the 8–10
decreased normalized startles in the gap
measures ANOVA on ranks within one
frequency of absolute startle data (with
gap or noise pulse versus without gap or
noise pulse, one mean value across trials
of 4 d per animal). Factors are group
gap” and “prepulse or no prepulse”), post
hoc all pairwise multiple comparisons
with Holm-Sidak, df ? 1, minimum p ?
0.001, maximum p ? 0.04.
recordings were made (average 16 d after the second exposure,
10–21 d, mean of individual animal’s ABR differences before
df ? 10, minimum p ? 0.111, maximum p ? 0.796), spontane-
ous rates (SRs) were significantly elevated in noise-exposed ani-
mals compared with control animals for units with CFs between
4 and 10 kHz (Fig. 3). Pairwise comparisons were made between
3, red crosses), between-subject effects “group noise-exposed or
maximum p ? 0.039.
Moreover, suprathreshold discharge rates were elevated for
tone levels up to 85 dB and CFs up to 16 kHz (Fig. 5). This
resulted in steeper RLFs for the noise-exposed animals especially
for tones above CF (Fig. 6). The difference was significant at all
below CF (ANOVA, between-subject effects “noise-exposed or
control” and “dB level” and interaction between both, adjust-
ment for multiple pairwise comparisons at 18 dB levels: Holm-
Sidak; above CF: corrected total df ? 5695, for 0–85 dB:
df ? 2843, for 45–85 dB: minimum p ? 0.001, maximum p ?
0.039; below CF: corrected total df ? 4239, for 55–85 dB: mini-
mum p ? 0.000, maximum p ? 0.033).
To explore changes in auditory-somatosensory integration in the
DCN after cochlear damage, rate differences between tone-
comparison was done for the immediate and long-term rate differ-
The immediate mean enhancement and suppression are
larger after noise exposure (Fig. 7A, left column graphs). This,
(Fig. 7B, left column pie charts), results in a greater bimodal
enhancement in the noise-exposed group compared with the
control animals (Fig. 7C, left column pie charts). Comparing the
immediate and long-term rate differences reveals a further in-
contrast, an increase in enhancement and especially suppression
graphs). At the same time the number of data points with long-
term enhancement is only slightly smaller than the number of
data points for the immediate rate differences in the noise-
(Fig. 7B, bottom row pie charts). This opposite shift of enhance-
ment and suppression between the noise-exposed and control
animals from the immediate to the long-term effects results in a
dominant long-term enhancement in noise-exposed animals,
contrasting with a dominant long-term suppression in control
animals (Fig. 7C, right column; Fig. 7A: significant difference of
the long-term effect between noise-exposed vs control indicated
with arrow and star; linear mixed model statistics, details see
methods/data analysis, adjustment for pairwise multiple com-
parisons: Sidak, df ? 140.942, p ? 0.000).
To assess the role of somatosensory-auditory integration in tin-
nitus, comparisons were made between the control animals and
octaves around CF) and below/above CF. RLFs of units with all CFs pooled. Control animals (black symbols; below CF, n ? 8
Effect of noise exposure on suprathreshold tone discharge rates. Mean RLFs recorded at unit CF (?0.1 up to 0.0
1664 • J.Neurosci.,February1,2012 • 32(5):1660–1671 Dehmeletal.•SomatosensoryTinnitus
tinnitus (Fig. 8). The mean immediate rate differences for the
8A, left column), whereas the no-tinnitus group showed larger
exceeding the effect of the noise exposure
animals stands out in terms of its long-
term bimodal effect: comparing the im-
mediate and long-term rate differences
reveals an increase in enhancement over
time in the tinnitus group (Fig. 8A, bot-
tom row). This results in a significant
difference between the immediate and
long-term data for the tinnitus group
across sound levels [Fig. 8A; significance
of linear mixed model statistics indicated
with arrow and star (for details see Mate-
rials and Methods, Data analysis); adjust-
ment for multiple pairwise comparisons:
from the immediate to the long-term rate
differences raises the mean rate enhance-
ment for the tinnitus group above the
level of enhancement for the control ani-
mals, resulting in a significant difference
control animals of the long-term rate dif-
ferences across level (Fig. 8A; compare
bottom with middle row graphs; signifi-
cance of linear mixed model statistics in-
dicated with arrow and star, adjustment
for multiple pairwise comparisons: Sidak,
df ? 104.295, p ? 0.000). The increase in
mean enhancement (Fig. 8A, bottom
row) together with an increase in the
number of data points with enhancement
a dominant long-term enhancement in
the tinnitus group (Fig. 8C, bottom pie
is characterized by a decrease in the mean
suppression and smaller increase in the
mean enhancement [Fig. 8A, top row
graphs: significance of linear mixed
model statistics is indicated with arrow
and star (for details see Materials and
Methods, Data analysis); adjustment for
multiple pairwise comparisons: Sidak,
df ? 1186.949, p ? 0.000]. The control
group shows an increase in suppression
and enhancement (Fig. 8A, middle row
graphs). Moreover, the control animals
number of data points with enhancement
and an increased number of data points
with suppression (Fig. 8B top and middle
of tinnitus animals, which shows an in-
creased number of data points with rate
enhancement. Together, these effects re-
matosensory (bimodal) enhancement in
the animals with tinnitus in contrast to control animals and ex-
posed no-tinnitus animals (Fig. 8B; significant differences be-
tween the animal groups’ long-term rate differences in linear
animals/108 RLFs). All RLFs were recorded at the units’ CF. Right, Long-term rate differences between the first tone RLF and a
second tone RLF recorded later in time after bimodal stimulation (control, n ? 8 animals/49 RLFs; noise-exposed, n ? 10
are collapsed across sound levels as pie charts in B and C. B, The number of data points with enhancement (white slices) or
Dehmeletal.•SomatosensoryTinnitus J.Neurosci.,February1,2012 • 32(5):1660–1671 • 1665
methods/data analysis, adjustment for
multiple pairwise comparisons: Sidak,
tinnitus vs control: df ? 104.295, p ?
0.000; tinnitus vs no-tinnitus: df ?
104.295, p ? 0.036).
Units were categorized based on the tem-
levels. The two major response types were
buildup and chopper (Fig. 9). In the tin-
nitus group, buildup units’ spontaneous
and tone-evoked rates were increased
compared with control animals and no-
tinnitus animals (Figs. 10, 11). The in-
crease was significant between 25 and 85
dB (Fig. 11, ANOVA, between-subject ef-
fects “tinnitus, no-tinnitus, control” and
“dB level” and interaction between both,
adjustment for multiple pairwise compari-
sons at 18 dB levels: Sidak, corrected total
df ? 596, control vs tinnitus, 25–85 dB:
This rate increase affected the onset and
buildup portion of the response and pro-
longed the response-duration (Fig. 11B).
Buildup units of the no-tinnitus animals
were not different from the control group.
In contrast to buildup units, chopper units
show increased SR (Fig. 10, ANOVA,
between-subject effects “tinnitus, no-
tinnitus, control” and “response type”
for pairwise multiple comparisons: Sidak,
corrected total df ? 112; buildup control
vs buildup tinnitus: p ? 0.026; buildup
no-tinnitus vs buildup tinnitus: p ?
0.005). In chopper units the increase of
sound-evoked rates in no-tinnitus ani-
mals were significantly different from the
12, ANOVA, between-subject effects
“tinnitus, no-tinnitus, control” and “dB
level” and interaction between both, ad-
justment for multiple pairwise compar-
isons at 18 dB levels: Sidak, corrected
total df ? 1025; control vs no-tinnitus,
40 dB: p ? 0.045, 45 dB: p ? 0.035).
In the tinnitus group, the long-term
somatosensory (bimodal) influence on
buildup units as well as chopper units
(Figs. 13, 14) was predominantly enhanc-
ing. Buildup units of the control and no-
tinnitus animals showed predominantly suppressive long-term
effects (Fig. 13). Chopper units in control animals showed pre-
dominantly suppressive long-term effects, whereas the chopper
units in no-tinnitus animals showed more balanced enhance-
ment and suppression (Fig. 14).
Although the low number of units did not allow a statistical
analysis within single response types and behavioral/noise ex-
posure groups, the long-term somatosensory effects of
buildup and chopper units (Figs. 13, 14) were similar to each
other. In both response types somatosensory (bimodal) enhance-
ment predominated in animals with tinnitus. This similarity
exists despite the different behavior of the tone and spontaneous
responses, which are only increased in buildup units (Figs.
exposed animals that developed tinnitus or with noise-exposed animals that did not develop tinnitus. Stars and arrows mark
1666 • J.Neurosci.,February1,2012 • 32(5):1660–1671Dehmeletal.•SomatosensoryTinnitus
This study is the first to investigate long-term effects of
somatosensory-auditory processing in vivo and its plasticity after
temporary noise-induced threshold shift. Long-term somatosen-
tem and highlights the importance of
incorporating the somatosensory sys-
tem into tinnitus treatment strategies.
Narrow band noise exposure resulted in
behavioral evidence of tinnitus in the
8–10 kHz. This correlates well with the
TTS between 6 and 16 kHz with a maxi-
studies showing the tinnitus spectrum
overlapping the hearing loss region
(Lockwood et al., 2002; Noren ˜a et al.,
erts et al., 2006; Schaette and Kempter,
octaves extending to frequencies ?10
kHz. Elevated ABRs at and above the ex-
posure frequency are commonly ob-
served after acoustic trauma(Brozoskiet
al., 2002; Kujawa and Liberman, 2009;
Mulders et al., 2011; Vogler et al., 2011).
The present study is the first to correlate
the frequency profile of elevated SR with the tinnitus frequency
sure band it was skewed to frequencies below the ABR threshold
elevations. This agrees with shifts in the noise-induced SR eleva-
tion of DCN neurons over time from frequencies below the ex-
posure frequency to higher frequency regions (Kaltenbach et al.,
2000). Our data show that tinnitus resides in bands at and above
elevated SRs reside precisely in CF regions of the tinnitus pitch
(Kaltenbach et al., 2004).
Although ABRs had recovered by the time of neural recordings,
DCN responses showed persistent increases in SRs and steeper
tone RLFs across the DCN unit population. The increased spon-
units in tinnitus animals. This corroborates previous results for
contrast, the chopper type in our study, which is comparable to
choppers shown in (Stabler et al., 1996), did not show increased
spontaneous and suprathreshold rates. In contrast to the steeper
RLFs shown here after TTS, ANF RLFs were shallower after TTS
(Kujawa and Liberman, 2009). While the shallower ANF slopes
may be due to deficient hair cell-ANF synapses, the steeper DCN
RLFs likely reflect central plasticity to counteract the reduced
ANF inputs (Cai et al., 2009; Schaette and Kempter, 2009;
Norena, 2011). Downregulation of inhibitory inputs accompa-
nying tinnitus after auditory insults (Wang et al., 2009; Middle-
ANOVA (p ? 0.05, adjustment for multiple comparisons: Sidak; for details, see Results).
n ? 2 animals/17 units, chopper tinnitus: n ? 3 animals/15 units, other control: n ? 6
animals/16 units, other no-tinnitus: n ? 3 animals/3 units, other tinnitus: n ? 3 animals/8
Dehmeletal.•SomatosensoryTinnitusJ.Neurosci.,February1,2012 • 32(5):1660–1671 • 1667
reduction in sideband inhibition could ex-
plain the larger increase in suprathreshold
The increase in tone-evoked responses
across frequency regions after TTS might
fects all frequencies (Anari et al., 1999;
Schaaf et al., 2003). Hyperacusis would
likely result in decreased normalized star-
tles as the gap carrier and noise-pulse are
both well above hearing threshold. In ad-
dition it would increase the absolute star-
pulse (Sun et al., 2009) as demonstrated
4). Tinnitus and hyperacusis often co-
occur (Anari et al., 1999; Schaaf et al.,
2003; Nelson and Chen, 2004; Dauman
occurring in the no-tinnitus group, their
effects on normalized startle responses in
the gap-PPI test could counteract each
acusis decreasing the normalized startle.
Whereas the immediate effects of trigem-
inal and dorsal column stimulation have
been described previously (Shore, 2005;
Shore et al., 2007; Kanold et al., 2011;
Koehler et al., 2011) long-term effects
have not been studied in vivo. In the pres-
ent study, bimodal enhancement or sup-
pression of sound-driven responses was
investigated ?35 min after repeated
auditory-somatosensory stimulation. This
timeframe is similar to that of long-term
depression and potentiation (LTD/LTP)
at the parallel fiber-cartwheel/fusiform
cell synapses in vitro (Fujino and Oertel,
2003; Tzounopoulos et al., 2004, 2007;
Zhao et al., 2011). Although LTP/LTD was
not shown at the auditory nerve-fusiform
synapses (Fujino and Oertel, 2003; Zhao et
the long-term bimodal effects on auditory
responses as consequences of long-term
synaptic plasticity at the parallel fiber syn-
apses. Assuming that spontaneously active
parallel fibers regulate fusiform and cart-
the parallel fiber synapses would modify
the excitability of the cells and hence
changes in postsynaptic excitability as con-
sequences or coeffects of LTP/LTD and the
(Dan and Poo, 2006; Doiron et al., 2011)
might also result in the long-term bimodal
In cerebellar-like circuits LTP/LTD
modifies parallel fiber input, thereby can-
1668 • J.Neurosci.,February1,2012 • 32(5):1660–1671Dehmeletal.•SomatosensoryTinnitus
2008). Plasticity of the parallel fiber input results in a “negative
image,” which is the inverse of the expected sensory input. In
electrosensory systems the negative image can be stored for at
least 38 min or until a changing parallel fiber input further mod-
ifies the negative image (Bell, 1986, 2001). The capability of
inputs’ plasticity to create negative images might underlie the
lasting effect of the bimodal stimulation on the acoustically
evoked responses. However in vivo studies of synaptic plasticity
are necessary to investigate plasticity and memory functions in
In contrast to control animals, which showed predominant bi-
modal suppression, long-term bimodal enhancement predomi-
nated after noise exposure, was especially prominent in tinnitus
animals, and was observed in chopper as well as buildup units.
Predominant bimodal suppression in control animals is consis-
tent with one proposed function of the somatosensory inputs, to
predominant bimodal enhancement after noise exposure points
to plastic changes affecting somatosensory inputs to the DCN,
which might result in tinnitus development: Strengthening of
excitatory, somatosensory inputs or increasing the sensitivity to
those inputs could reflect homeostatic plasticity of multisensory
al., 2005; Schaette and Kempter, 2009; Zeng et al., 2009; Norena,
2011) after reduction of ANF input (Kujawa and Liberman,
2009). The differential expression of distinct vesicular glutamate
lows for examining this theory. Whereas ANF synapses in the
deep layer of DCN express VGLUT1, non-auditory, glutamater-
weeks after unilateral cochlear damage, VGLUT2 immunoreac-
tivity was upregulated and VGLUT1 downregulated in the ipsi-
lateral cochlear nucleus (Zeng et al., 2009). Upregulation of
somatosensory inputs to granule cells, which innervate fusiform
cells, could explain the increased bimodal enhancement after
and epilepsy, both characterized by hyperexcitability, show in-
creased VGLUT2 expression (Walle ´n-Mackenzie et al., 2010),
suggesting that upregulation of VGLUT2 expression in auditory
centers might lead to hyperexcitability underlying tinnitus. In-
deed, increased responsiveness to somatosensory stimulation
was demonstrated after broad-band noise exposure and perma-
nent threshold shifts: thresholds and latencies to trigeminal gan-
glion stimulation were decreased and the response amplitudes
Dehmeletal.•SomatosensoryTinnitus J.Neurosci.,February1,2012 • 32(5):1660–1671 • 1669
increased (Shore et al., 2008). These findings are paralleled by
heightened responses to somatosensory stimulation in tinnitus
patients demonstrated by fMRI (Lanting et al., 2010). Increased
excitatory somatosensory drive to DCN neurons could explain
why loudness and pitch of tinnitus can be changed by somato-
sensory stimulation in the face, head and neck regions (Pinchoff
specific group of neurons with increased sensitivity to somato-
sensory inputs, somatosensory stimulation would change the re-
The shift toward bimodal enhancement occurred in both
buildup and chopper units, suggesting an enhancement of so-
matosensory input across unit types. In contrast, the increases in
tone-evoked responses and spontaneous activity were only ob-
the initial membrane potentials of these two unit types (Kanold
and Manis, 1999), leading to differential effects of enhanced so-
matosensory inputs (Zeng et al., 2009) on sound-driven activity.
An increase in somatosensory-evoked DCN discharges after
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