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Neuroscience 167 (2010) 567–572
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PECIFIC AND RAPID EFFECTS OF ACOUSTIC STIMULATION ONHE TONOTOPIC
DISTRIBUTION OF Kv3.1b POTASSIUM CHANNELS
N THE ADULT RAT
Kca2KCspeoehKKahsqCt2mpta
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. G. STRUMBOS,a D. B. POLLEYb1 AND
. K. KACZMAREKa*
Departments of Pharmacology, Cellular and Molecular
Physiology,ale University School of Medicine, New Haven, CT 06511,
USA
Vanderbilt Kennedy Center for Research on Human
Development,epartment of Hearing and Speech Sciences, Vanderbilt
Bill Wilker-on Center for Otolaryngology and Communication
Sciences, Vander-ilt University School of Medicine, Nashville, TN
37232, USA
bstract—Recent studies have demonstrated that total cel-ular
levels of voltage-gated potassium channel subunits canhange on a
time scale of minutes in acute slices and cul-ured neurons, raising
the possibility that rapid changes inhe abundance of channel
proteins contribute to experience-ependent plasticity in vivo. In
order to investigate this pos-ibility, we took advantage of the
medial nucleus of the trap-zoid body (MNTB) sound localization
circuit, which containseurons that precisely phase-lock their
action potentials toapid temporal fluctuations in the acoustic
waveform. Previ-us work has demonstrated that the ability of these
neu-ons to follow high-frequency stimuli depends criticallypon
whether they express adequate amounts of the potas-ium channel
subunit Kv3.1. To test the hypothesis that netmounts of Kv3.1
protein would be rapidly upregulated whennimals are exposed to
sounds that require high frequencyring for accurate encoding, we
briefly exposed adult rats tocoustic environments that varied
according to carrier fre-uency and amplitude modulation (AM) rate.
Using an anti-ody directed at the cytoplasmic C-terminus of Kv3.1b
(thedult splice isoform of Kv3.1), we found that total
cellularevels of Kv3.1b protein—as well as the tonotopic
distributionf Kv3.1b-labeled cells—was significantly altered
following0 min of exposure to rapidly modulated (400 Hz)
soundselative to slowly modulated (0–40 Hz, 60 Hz) sounds.
Theseesults provide direct evidence that net amounts of
Kv3.1brotein can change on a time scale of minutes in response
totimulus-driven synaptic activity, permitting auditory neu-ons to
actively adapt their complement of ion channels tohanges in the
acoustic environment. © 2010 IBRO. Pub-ished by Elsevier Ltd. All
rights reserved.
ey words: fragile X mental retardation protein (FMRP),
localrotein synthesis, medial nucleus of the trapezoid bodyMNTB),
auditory brainstem, amplitude modulation, calyx ofeld.
Present address: Eaton-Peabody Laboratory, Massachusetts Eyend
Ear Infirmary, Boston, MA 02114, USA.Corresponding author. Tel:
�1-203-785-4500; fax: �1-203-785-5494.-mail address:
[email protected] (L. K. Kaczmarek).bbreviations: AM,
amplitude modulation; au, arbitrary units; DMR,ynamic moving
ripple; FMRP, fragile X mental retardation protein; Hz,
tHz, hertz, kilohertz; MNTB, medial nucleus of the trapezoid
body; OD,ptical density; SPL, sound pressure level.
306-4522/10 $ - see front matter © 2010 IBRO. Published by
Elsevier Ltd. All rightoi:10.1016/j.neuroscience.2010.02.046
567
v3.1 is a voltage-gated potassium channel subunit that isritical
for repetitive high-frequency action potential gener-tion (Gan and
Kaczmarek, 1998; Rudy and McBain,001). The Kv3.1 gene gives rise to
two splice isoforms,v3.1a and Kv3.1b, which differ in the length of
their-terminal domains (Luneau et al., 1991). The longerplice
variant, Kv3.1b, is regulated by protein kinase C andredominates in
the mature nervous system (Kaczmarekt al., 2005). The principal
neurons of the medial nucleusf the trapezoid body (MNTB) which
require this channel toncode rapid temporal modulations in auditory
stimuli,ave proven to be a useful model for understanding howv3.1b
is regulated. Previous work has demonstrated thatv3.1b protein
levels and current amplitudes vary system-tically across the
tonotopic axis of the MNTB, with theighest levels of the channel in
the medial end, corre-ponding to neurons that respond selectively
to high-fre-uency sounds (Li et al., 2001; Brew and Forsythe,
2005).hronic lack of sensory input results in the loss of this
onotopic gradient (von Hehn et al., 2004; Leao et al.,006),
however the extent to which the gradient can beodified by sensory
experience is unknown. We now re-ort that the tonotopic
distribution of Kv3.1b changes on aime scale of minutes in response
to specific features of thembient sound environment.
EXPERIMENTAL PROCEDURES
coustic stimulation
wenty-seven awake adult (8–12 week-old) Sprague–Dawleyats
(Charles River Laboratories, Wilmington, MA, USA) werexposed to
amplitude modulation (AM) stimuli for a 30 min periodt 65 dB sound
pressure level (SPL) in a small sound attenuatinghamber. All
experimental protocols involving animals were ap-roved by the Yale
University Animal Use and Care Committee.rotocols were carefully
designed to minimize both the number ofnimals used and their
suffering. A total of six stimuli were used inhe study (Fig. 1).
Stimuli were centered on either 4 kHz or 32 kHzarrier frequencies
and one of three AM envelope conditions: aow AM rate dynamic moving
ripple (0–40 Hz; dynamic movingipple (DMR), Escabi and Schreiner,
2002), intermediate AM rate57–63 Hz), or high AM rate (380–420 Hz).
Rats were randomlyeparated into six groups: group 1a (X1�4 kHz,
X2�0–40 Hz,�4), group 2a (X1�4 kHz, X2�57–63 Hz, n�4), group 3a
(X1�4Hz, X2�380–420 Hz, n�5), group 1b (X1�32 kHz, X2�0–40z, n�5),
group 2b (X1�32 kHz, X2�57–63 Hz, n�5), and groupb (X1�32 kHz,
X2�380–420 Hz, n�4), where X1 is the carrier
requency on which stimuli were centered, X2 is the
envelopeodulation range, and n is the number of rats. At the final
minutef acoustic exposure, the exposure chamber was flooded
with
soflurane (5% in oxygen) and rats were quickly and silently
eu-
hanized with a lethal dose of pentobarbital sodium followed
by
s reserved.
mailto:[email protected]
-
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J. G. Strumbos et al. / Neuroscience 167 (2010) 567–572568
ranscardial perfusion with 0.1 M phosphate-buffered saline
(PBS)ollowed by fixative (4% paraformaldehyde in 0.1 M
phosphateuffer, pH 7.4). Following post-fixation for 2 h at 4 C,
brainstemections were cryoprotected in a solution of 30% sucrose in
0.1 MBS and flash frozen on dry ice.
mmunofluorescence
rozen brains were labeled using an encrypted code such that
thenvestigator responsible for tissue processing was fully
blindedith respect to stimulus condition. Sections (35 �m) were
pre-ared on a Leica CM 3050-S cryostat and mounted onto glasslides
coated with poly-L-lysine (Sigma–Aldrich, St. Louis, MO,SA).
Sections were then permeabilized for 24–48 h in a blockingolution
containing 0.5% Triton-X 100% and 1% goat serum inBS. Subsequently,
sections were incubated with a rabbit poly-lonal antibody directed
at the cytoplasmic C-terminus of Kv3.1bor 60 h at 4 C (1:500 in
blocking solution; antibody production andalidation described in
Perney and Kaczmarek, 1997). For sec-ndary labeling, sections were
incubated with Alexa Fluor 488oat anti-rabbit IgG (1:500 in
blocking solution, Molecular Probes,ugene, OR, USA) for 1–2 h at
room temperature. Following
mmunolabeling, MNTB sections were scanned using a Zeiss LSM10
laser scanning confocal microscope system.
ata analysis
igital image quantification was carried out using ImageJ
softwarey a blinded investigator, with sections (n�99) from each of
the sixxperimental groups randomly interspersed. Images were
normal-
zed by background subtraction (Roll Ball Radius�50 pixels)
andthreshold of 115 a.u. (on a scale of 0–255) was set for cell
dentification. Cells were outlined using a particle analysis
algo-ithm (Minimum radius�50 pixels) and images were
carefullyxamined by a blinded investigator to exclude artifacts. In
calcu-
ating mean cell optical density (O.D.), we restricted our
analysiso animals for which a minimum of three sections containing
theNTB were available (n�27). To ensure that each animal wasqually
represented in our calculation, three sections were se-
ected for each animal using the strict criterion that they
containhe greatest number of identified MNTB neurons among all
sec-
ig. 1. Illustrations of auditory stimuli. (a) Spectrogram of the
complexontrol stimulus (dynamic moving ripple; “DMR”) composed of
0.5ctave-wide sounds centered on either low (3.36–4.76 kHz; “4
kHz”)r high (26.9–38.06 kHz; “32 kHz”) frequencies. The DMR is
smoothlynd randomly modulated both in time (0–40 Hz) and frequency
(spec-
ral contrast between 0 and 0.5 cycles/octave). Scale bars
represents and 0.25 octaves along the horizontal and vertical arms,
respec-
ively. (b) AM sound stimuli were carried by either 4 or 32 kHz
pureones and modulated at either low rates (60�5% Hz) or high
rates400�5% Hz). For interpretation of the references to color in
this figureegend, the reader is referred to the Web version of this
article.
ions for that animal. This selection was made by an investigator
H
ho was blinded with respect to the stimulus condition of
thenimal. Thus, the calculation of mean optical density per cell
wasarried out on 84 separate sections, which yielded a total
of0,512 cells. For calculations of medial-to-lateral ratios and
con-truction of tonotopic probability distributions, all MNTB
sectionsere used (n�99).
RESULTS
n vivo single-unit studies have demonstrated that MNTBrincipal
neurons synchronize their action potentials to thehase of AM sound
stimuli across a wide range of modu-
ation rates (Joris and Yin, 1998; Kadner and Berrebi,008;
Kopp-Scheinpflug et al., 2008), making it possible torecisely
control their activity patterns in vivo by exposingnimals to AM
sounds. In vitro, MNTB neurons from ani-als lacking the Kv3.1 gene
can readily follow 60 Hz
timulation, but are incapable of following higher rates
oftimulation such as 400 Hz (Macica et al., 2003). Thus,hile Kv3.1b
subunits are not expected to be required forNTB neurons to follow
AM sounds modulated at 60 Hz,igh levels of Kv3.1b current should be
absolutely neces-ary for MNTB neurons to follow AM stimulus rates
such as00 Hz. To test the hypothesis that Kv3.1b protein levelsould
be rapidly upregulated in vivo following exposure to
ast—but not slow—amplitude modulation, we exposed 27dult (8–12
week old) rats to AM sound stimuli for a 30 mineriod (Fig. 1). To
test the corollary hypothesis that suchhanges would be spatially
specific, we took advantage ofhe tonotopic organization of the MNTB
by using low (4Hz) versus high (32 kHz) pure tone carrier
frequencies toarget lateral versus medial regions of the MNTB,
respec-ively. At each carrier frequency, the temporal envelope ofhe
stimulus was amplitude modulated at either low rates60�5% Hz; “60
Hz AM”) or high rates (400�5% Hz; “400z AM”). We tested the
possibility that Kv3.1b expressionas specifically related to rapid
temporal modulation of thecoustic stimulus, and not its overall
complexity, by expos-
ng control rats to the DMR, a frequency-modulated stim-lus
(0–0.5 cycles/octave spectral contrast) with a broadange of low
frequency temporal modulations (0–40 Hz)entered either on low
(4�0.5 kHz octaves; “4 kHz”) origh (32�0.5 kHz octaves; “32 kHz”)
carrier frequenciesEscabi and Schreiner, 2002). Animals were
randomly di-ided into six groups corresponding to the six
stimulationonditions, with four to five animals in each group.
Allissue processing and digital image quantification was car-ied
out by an investigator blind to the animal’s
stimulationondition.
To address the first hypothesis—that Kv3.1b proteinevels
increase in vivo following exposure to rapid ampli-ude
modulation—we compared the mean intensity ofv3.1b immunoreactivity
in the MNTB after 30 min ofound exposure. MNTB images from each
stimulus groupere pooled (n�81) and mean cell O.D. was computed
detailed methods in “Experimental Procedures”). At bothhe 4 kHz
and 32 kHz carrier frequencies, Kv3.1b immu-oreactivity was
significantly enhanced when sounds weremplitude modulated at 400 Hz
compared to either the 60
z or DMR conditions (Fig. 2a, b; one-way ANOVA with
-
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KMtq5Ktaf
gq(CtKtthts
ppt
FilhTNbP(pa .25 �m.
J. G. Strumbos et al. / Neuroscience 167 (2010) 567–572 569
onferroni post-hoc test, P�0.01). We also observed aignificant
interaction between carrier frequency andodulation rate, such that
maximal Kv3.1b labeling waschieved when the high frequency tone was
modulatedt the fastest rate (two-way ANOVA with Bonferroniost-hoc
test, P�0.001).
We tested the second hypothesis—that changes inv3.1b levels are
localized to specific regions of theNTB—by quantifying the pattern
of Kv3.1b immunoreac-
ivity in animals exposed to 4 versus 32 kHz carrier fre-uencies.
Each MNTB section (n�99) was divided into50 �m halves along the
tonotopic axis and the number ofv3.1b-immunoreactive cells in each
half was quantified. A
onotopic ratio (medial immunoreactivity/lateral
immunore-ctivity) was calculated for each section, and all
sections
140
145
150
155
*
).u.a(ytisnedlacitpo
naeM
**
RMD:zHk4
MAzH06:zHk4
MAzH004:zHk4
RMD:zHk23
MAzH06:zHk23
MAzH004:zHk23
b##
Medial Lateral Medial L
a
32 kHz: DMR 32 kHz: 60 Hz AM
4 kHz: 60 Hz AM4 kHz: DMR
Medial Lateral
Medial Lateral
Medial
Medial
ig. 2. Effects of sound amplitude modulation and carrier
frequency ontensity of Kv3.1b labeling in representative MNTB
sections from ratsabeling intensity following 30 min of acoustic
stimulation varies accordighest levels of Kv3.1b immunoreactivity
observed when the high-freqhe number of cells (N) in each stimulus
condition were as follows: N (4(32 kHz: DMR)�1970; N (32 kHz: 60 Hz
AM)�2430; N (32 kHz: 400
oth a one-way and two-way ANOVA followed by Bonferroni
post-ho�0.001 compared to other 32 kHz stimuli; ## indicates
two-way
c) High-magnification confocal images of Kv3.1b
immunofluorescenceattern of Kv3.1b immunofluorescence was
consistent with the channel., 2003) and did not vary across
stimulation conditions. Scale bar: 0
rom each stimulus group were then pooled to compute a
roup means. As stated above, low (4 kHz) carrier fre-uencies
target the lateral region of the MNTB while high32 kHz) carrier
frequencies target the medial region.onsistent with our hypothesis,
we found that in each of
he 4 kHz conditions, the medial-to-lateral ratio
ofv3.1b-immunoreactive cells was lower than the medial-
o-lateral ratios observed in rats exposed to 32 kHzones (Fig.
3a; two-way ANOVA with Bonferroni post-oc test, P�0.01). The number
of Kv3.1b-immunoreac-ive cells per section did not vary
significantly betweentimulus conditions (��92, ��34).
To facilitate comparisons of Kv3.1b immunoreactivityatterns
throughout the entire MNTB, we determined therecise locations of
all Kv3.1b-immunoreactive cells alonghe tonotopic axis in each
section, then pooled together all
Medial Lateral
0
255
32 kHz: 400 Hz AM
4 kHz: 400 Hz AM
32 kHz: 400 Hz AM
l
l
Medial Lateral
Medial Lateral
400 Hz AMDMR 60 Hz AM
z
z
Opt
ical
den
sity
(a.u
.)
levels in the MNTB. (a) Pseudocolor images showing the pattern
andg to each of the six stimulus groups. Scale bar: 100 �m. (b)
Kv3.1bth the carrier frequency and modulation rate of the stimulus,
with thee is modulated at the fastest rate. Data are presented as
means�SE.R)�1333; N (4 kHz: 60 Hz AM)�1763; N (4 kHz: 400 Hz
AM)�1481;1535. Differences between groups were statistically
evaluated usings. * indicates P�0.01 compared to other 4 kHz
stimuli; ** indicates
on of P�0.001 between carrier frequency and modulation
rate.ntative cells from each sound stimulation condition. The
subcellularmembrane and cytoplasmic localization (Li et al., 2001;
Elezgarai et
ateralLatera
Latera
c
4 kH
32 kH
n Kv3.1bbelongining to bo
uency tonkHz: DMHz AM)�
c analyseinteracti
in represel’s known
vailable cells from each stimulus condition (N�9688). We
-
tslFsiSPttsklHlupe
Td
utepKcisKcpwnOcmcamca
FKrnDdoiaN lor in this
J. G. Strumbos et al. / Neuroscience 167 (2010) 567–572570
hen created a tonotopic probability distribution for eachtimulus
representing the relative proportion of Kv3.1b-abeled cells in 50
�m-wide bins along the tonotopic axis.or all three amplitude
modulation conditions, there was aignificant difference between the
two carrier frequenciesn the median location of identified cells
(Kolmogorov–mirnov test, DMR: P�0.001; 60 Hz: P�0.02; 400
Hz:�4.0�10�12). Whereas the tonotopic probability distribu-
ion was only weakly influenced by carrier frequency whenhe
stimulus was modulated slowly (DMR and 60 Hz), ithifted
dramatically toward the medial end when the 32Hz stimulus was
modulated at 400 Hz and toward the
ateral end when the 4 kHz stimulus was modulated at 400z (Fig.
3b). This observation, as well as our finding that
abeling intensity was significantly enhanced by both stim-li at
400 Hz, suggests that Kv3.1b levels in MNTB princi-al neurons are
increased selectively by rapid temporalnvelope modulations.
DISCUSSION
he amount of Kv3.1b current in an MNTB principal neuron
0.00
0.04
0.08
0.12
Pro
porti
on o
f cel
ls
Med
60 Hz
250
Medial Lateral (µm)
Dynamic moving ripple (0-40 Hz)
32 kHz 4 kHz
250 500 750 1000
b
4 kHz: DMR
4 kHz: 60 Hz AM
4 kHz: 400 Hz AM
32 kHz: DMR
32 kHz: 60 Hz AM
32 kHz: 400 Hz AM
Medial
a
*
ig. 3. Effects of carrier frequency on distribution of Kv3.1b
immunorev3.1b-labelled cells varies according to the carrier
frequency of the st
epresents the average medial-to-lateral ratio across all groups
(1.30�(4 kHz: DMR)�15; n (4 kHz: 60 Hz AM)�14; n (4 kHz: 400 Hz
AM)�1ifferences between groups were statistically evaluated using a
twemonstrate that the 400 Hz AM stimuli had a stronger effect
(D�0.15)r the DMR (D�0.076) stimuli. * indicates P�0.02, *****
indicates P�4.
n each distribution (solid lines represent 32 kHz stimuli,
dotted lines res follows: N (4 kHz: DMR)�1384; N (4 kHz: 60 Hz
AM)�1637; N (4 k(32 kHz: 400 Hz AM)�1118. For interpretation of the
references to co
etermines its ability to follow high rates of synaptic stim-
t
lation (Macica et al., 2003; Song et al., 2005). One es-ablished
mechanism by which Kv3.1b currents becomenhanced to permit high
frequency firing is through de-hosphorylation at Ser503 (Macica et
al., 2003). Whereasv3.1b is basally phosphorylated at Ser503 under
quiet/ontrol conditions, it undergoes dephosphorylation follow-
ng seconds to minutes of auditory stimulation in vivo orynaptic
stimulation in vitro (Song et al., 2005; Song andaczmarek, 2006).
It is not clear, however, whetherhanges in the phosphorylation
state of the protein canrovide a persistent enhancement of K�
currents norhether post-translational modification alone
provideseurons with an adequate dynamic range of Kv3.1 current.ur
present results provide evidence that levels of Kv3.1b
hannel subunits, which serve to rapidly repolarize theembrane
potential during trains of high-frequency firing,
an become altered within 30 min of a change in theuditory
environment. Although we are not able to deter-ine the time course
over which these newly synthesized
hannels are inserted into the plasma membrane in vivo,n increase
in Kv3.1b membrane expression would serve
Lateral (µm)
e modulation
4 kHz
750 1000
Medial Lateral (µm)250 500 750 1000
400 Hz amplitude modulation
32 kHz 4 kHz
ratio
*
*****
long the tonotopic axis of the MNTB. (a) The medial-to-lateral
ratio ofata are presented as means�SE. * indicates P�0.01. The
dotted linehe number of sections (n) in each stimulus condition
were as follows:Hz: DMR)�19; n (32 kHz: 60 Hz AM)�23; n (32 kHz:
400 Hz AM)�13.OVA. (b) Probability histograms of pooled cells in
each condition
istributions of Kv3.1 in the MNTB than either the 60 Hz AM
(D�0.049). Lines above the probability histograms span the median
50% of cellskHz stimuli). The number of cells (N) in each stimulus
condition werez AM)�1475; N (32 kHz: DMR)�1828; N (32 kHz: 60 Hz
AM)�2264;figure legend, the reader is referred to the Web version
of this article.
ial
amplitud
32 kHz
500
-to-lateral
*
activity aimulus. D0.08). T
5; n (32 ko-way ANon the d
0�10�12
present 4Hz: 400 H
o maintain the increase in Kv3.1b current that is triggered
-
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efc3(nM2llusdeagft3iacm1
b1mKMmremt2eaaildu2aKfnPKp
pfmb(cKsangmgTwhs
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J. G. Strumbos et al. / Neuroscience 167 (2010) 567–572 571
y dephosphorylation of pre-existing Kv3.1b channels, andllow the
neurons to maintain firing action potentials atigh rates. Direct
measurements of changes in Kv3.1brotein in the plasma membrane will
require either electronicroscopic techniques or in vitro brain
slice models of this
n vivo phenomenon to quantify expression by approachesuch as
surface biotinylation.
Previous in vivo studies examining the effects of affer-nt
activity on Kv3.1 protein levels in central neurons haveocused on
chronic sensory deprivation. In the avian nu-leus magnocellularis,
Kv3.1 protein levels decline withinh of cochlear ablation and
return to baseline within 24 h
Lu et al., 2004). Additionally, it has been shown that theormal
tonotopic gradient in Kv3.1b levels within theNTB is absent in both
congenitally deaf mice (Leao et al.,006) and in mice that gradually
lose hearing throughout
ife (von Hehn et al., 2004). In the developing visual
cortex,ong-term sensory deprivation by dark rearing results in
anpregulation in Kv3.1b and Kv3.2 protein levels in fast-piking
cortical basket cells that can be observed within 30ays (Grabert
and Wahle, 2009). To the best of our knowl-dge, however, the
present study is the first to report rapidlterations of the gross
anatomical distribution of a voltage-ated ion channel in adult
animals in response to specificeatures of sensory stimuli. The most
striking aspect ofhese results is the exceedingly short time course
of only0 min over which auditory stimulation altered Kv3.1b
mmunoreactivity in the MNTB, which is comparable tomount of time
required to observe stimulus-inducedhanges in immunoreactivity for
proteins encoded by im-ediate early genes such as c-Fos (e.g.
Graybiel et al.,990).
Activity-dependent regulation of Kv3.1b mRNA haseen shown to
require 6 h in vitro (Liu and Kaczmarek,998), therefore it seems
unlikely that transcriptionalechanisms can contribute to such rapid
adjustment ofv3.1b levels during brief periods of sound
stimulation.oreover, we performed all immunohistochemistry
onembrane-permeabilized tissue using an antibody di-
ected at the cytoplasmic C-terminus of the channel,
whichliminates the possibility that the increase in Kv3.1b
im-unoreactivity resulted from activity-dependent protein
rafficking (Misonou et al., 2004; Misonou and Trimmer,004; Kim
et al., 2007). Our findings are most readilyxplained by a rapid
increase in Kv3.1b protein synthesisnd/or turnover in response to
stimulus-evoked synapticctivity. This hypothesis is consistent with
recent findings
n hippocampal slices and cultured neurons indicating thatevels
of the voltage-gated potassium channel Kv1.1 inendrites can be
rapidly altered by activity-dependent reg-lation of local protein
synthesis (Raab-Graham et al.,006). Moreover, although Kv3.1
protein expression varieslong the tonotopic axis, there appears to
be no gradient ofv3.1 mRNA in the MNTB, indicating that, as has
been
ound for many other proteins, levels of Kv3.1b subunits doot
directly reflect levels of its mRNA (Perney et al., 1992;erney and
Kaczmarek, 1997; Li et al., 2001). Intriguingly,v3.1 mRNA has been
identified as a candidate binding
artner for fragile X mental retardation protein (FMRP), a
rotein that regulates rapid activity-dependent translationrom
preexisting mRNAs (Darnell et al., 2001). Electronicroscopy studies
have shown that Kv3.1b is present onoth pre- and post-synaptic
membranes in the MNTBElezgarai et al., 2003), raising the
possibility that FMRPould mediate local activity-dependent
translation ofv3.1b in synaptic terminals as well as in the
postsynapticomata. An increase in pre-synaptic Kv3.1b would result
inction potential narrowing and a decrease in the amount
ofeurotransmitter released for each spike. These data sug-est that
rapid adjustments in intrinsic electrical excitabilityay compliment
established contributions from ligand-ated receptor dynamics (von
Gersdorff and Borst, 2002;akahashi et al., 2003; Sarro et al.,
2008) and local net-ork plasticity (Dean et al., 2008; Polley et
al., 2004) as aomeostatic mechanism to link cellular excitability
to sen-ory experience.
cknowledgments—This work was supported by National Insti-utes of
Health (NIH) grants DC001919 (L.K.K.) and DC009488D.B.P.). We thank
Gregory Derderian for technical assistancend Christian von Hehn for
critical reading of the manuscript.
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(Accepted 18 February 2010)(Available online 26 February
2010)
SPECIFIC AND RAPID EFFECTS OF ACOUSTIC STIMULATION ON THE
TONOTOPIC DISTRIBUTION OF Kv3.1b POTASSIUM CHANNELS IN THE ADULT
RATEXPERIMENTAL PROCEDURESAcoustic
stimulationImmunofluorescenceData analysis
RESULTSDISCUSSIONAcknowledgmentsREFERENCES
