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The Journal of Neuroscience, July 1, 2002, 22(13):5271-5276
BRIEF COMMUNICATION
Absence of Long-Term Depression in the Visual Cortex of Glutamic
Acid Decarboxylase-65 Knock-Out Mice
Se-Young
Choi1, *,
Bernardo
Morales1, *,
Hey-Kyoung
Lee2, and
Alfredo
Kirkwood1
1 Department of Neuroscience and 2 Howard
Hughes Medical Institute, Mind Brain Institute, Johns Hopkins
University, Baltimore, Maryland 21218
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ABSTRACT |
Long-term depression (LTD) is widely considered a mechanism for
experience-induced synaptic weakening in the brain. Recent in
vivo studies on glutamic acid decarboxylase [GAD 65 ( /)] knock-out mice indicates that GABAergic synaptic inhibition is also
required for the normal weakening of deprived inputs in the visual
cortex. To better understand how GABAergic inhibition might control
plasticity, we assessed the status of synaptic inhibition and LTD in
visual cortical slices of GAD 65 knock-out mice. We found the
following: (1) the efficacy of GABAergic synapses during repetitive
activation is reduced in GAD 65 (/) mice; (2) the induction of LTD
is impaired in the visual cortex of GAD 65 (/) mice; and (3)
chronic, but not acute, treatment with the benzodiazepine agonist
diazepam restores LTD in GAD 65 (/) mice. These results suggest
that a certain inhibitory tone is required for the induction of LTD in
visual cortex. We propose that the lack of visual cortical LTD in GAD
65 (/) may account for the lack of experience-dependent plasticity
in these mice.
Key words:
critical period; synaptic plasticity; GABA; neocortex; IPSC; synaptic inhibition
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INTRODUCTION |
Shortly
after birth, the visual cortex enters into a brief critical period of
enhanced plasticity (Hubel and Wiesel, 1970 ). At this stage, a simple
alteration of visual experience, such as monocular deprivation,
selectively weakens the deprived inputs, shifting the eye preference of
cortical cells toward the nondeprived eye (Fagiolini et al., 1994;
Gordon et al., 1996). It is widely believed that NMDA
receptor-dependent forms of synaptic modification, such as long-term
potentiation (LTP) and long-term depression (LTD), are essential for
developmental plasticity in the visual and other sensory cortices
(Singer, 1995; Daw et al., 1999; Rittenhouse et al., 1999; Di Cristo et
al., 2001). In the context of this idea, it has been proposed that the
critical period results from the delayed maturation of the GABAergic
system (Komatsu, 1983; Kirkwood and Bear, 1994). The recruitment of
GABAergic synaptic inhibition restricts the induction of synaptic
plasticity (Kirkwood and Bear, 1994); hence, its late maturation (Blue
and Parnavelas, 1983; Luhmann and Prince, 1991; Guo et al., 1997) would
provide a window of opportunity for plasticity to occur (Huang et al., 1999; Rozas et al., 2001).
Recently, however, this view has been challenged based on results
obtained with knock-out (KO) mice that lack glutamic acid decarboxylase
65 (GAD 65), one of the two isoforms of the GABA synthesizing enzyme
GAD 65. In GAD 65 (/) mice, monocular deprivation does not cause
the normal shift in ocular dominance unless synaptic inhibition is
pharmacologically enhanced by local application of diazepam (Hensch et
al., 1998). Although these results stress the importance of GABAergic
inhibition in visual plasticity, the cellular basis for the lack of
plasticity in GAD 65 (/) mice remains unknown. The
induction of LTP and LTD in visual cortical slices from GAD 65 (/)
mice was reportedly normal, supporting arguments against the
involvement of these mechanisms of synaptic modification in visual
cortical plasticity. In view of the important implications of such a
conclusion, we set out to reexamine in GAD 65 (/) mice the status
of LTD, perhaps the most relevant mechanism of plasticity to account
for the effects of monocular deprivation. Here we report that the
induction of LTD is impaired in young GAD 65 (/) mice, yet LTD can
be restored in these mice by chronic application of diazepam. Our
reexamination of the status of NMDA-dependent plasticity forces a
fundamental revision in how in vivo experiments on GAD 65 (/) are interpreted.
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MATERIALS AND METHODS |
Coronal slices (300-400 µm) from the visual cortex and
hippocampus of GAD 65 (/) mice (Kash et al., 1997) were prepared as
described previously (Kirkwood and Bear, 1994). Briefly, after sectioning in ice-cold oxygenated (95% O2-5%
CO2) dissection buffer (in mM: 212.7 sucrose, 5 KCl, 1.25 NaH2PO4, 3 MgCl2, 1 CaCl2, 26 NaHCO3, 10 dextrose, and 10 kynurenate), slices
were transferred to a storage chamber containing normal artificial CSF
(ACSF) for at least 1 hr before recording. Normal ACSF is similar to
the dissection ACSF except that sucrose is replaced by 124 mM NaCl, MgCl2 is lowered to 1 mM, CaCl2 is raised to 2 mM, and kynurenate is omitted.
For whole-cell voltage clamp, the cells were visually identified with
an infrared differential interference contrast Zeiss (Oberkochen, Germany) microscope. Patch pipettes (2-4 M )
were filled with internal solution consisting of (in mM):
130 Cs-gluconate, 8 KCl, 10 EGTA, 10 HEPES, and 1 QX-314, pH 7.4 (275-285 mOsm). In the experiments described in Figure 2, 40 mM Cs-gluconate was replaced by 40 mM CsCl. The
reversal potential of the GABAergic currents was close to the value
predicted by the Nernst potential of Cl
(64.6 ± 2.0 mV, n = 5 and 30.5 ± 1.3 mV, n = 4 for the first and second solutions,
respectively). The junction potential (typically <5 mV) was
compensated. Only cells with membrane potentials more negative than
65 mV, access resistance smaller than 20 M (8-18 M,
compensated at 80%), and input resistance larger than 100 M
(130-410 M) were studied.
Synaptic responses were evoked with 15-300 µA, 0.2 msec current
pulses delivered with a bipolar stimulating electrode (200 µm
diameter; Frederick Haer Co., Bowdoinham, ME). Microelectrodes were filled with ACSF (1-2 M) for extracellular recordings. In visual cortical experiments, the stimulating electrodes were placed in
the middle of the cortical thickness, approximately equidistant from
the pia and the white matter, and the responses were recorded in layers
II/III. In hippocampal experiments, the stimulating and the recording
electrodes were places in the dendritic field of the CA1 region.
Synaptic responses were quantified as the initial slope of the field
potential (FP) in CA1 and the amplitude of the maximum negative
FP in layer III. Changes in the amplitude of the maximum negative FP
reflect changes in the magnitude of a synaptic current sink (Aizenman
et al., 1996) and correlate with changes in the initial slope of EPSPs
recorded intracellularly in layer III neurons (Kirkwood and Bear,
1994). Long-term depression was induced by delivering 900 pulses at 1 Hz. Only data from slices with stable recordings (<5% change over the
baseline period) were included in the analysis. All data are presented
as average ± SEM normalized to the preconditioning baseline.
Statistical significance was assessed using t test or
two-way repeated-measures ANOVA, followed by the Fisher's post
hoc test. Diazepam was dissolved in 0.01% DMSO. All drugs were
purchased from Sigma/RBI (Poole, UK).
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RESULTS |
All experiments were performed in visual cortical slices prepared
from 3-week-old [postnatal day 21 (P21) to P27] GAD 65(/) mice
and age-matched wild-type littermates. Stimulation was applied to layer
IV, and synaptic responses were recorded in layer II/III.
Normal inhibitory input in GAD 65 (/) mice
Indirect evidence from field recordings and
high-K-induced GABA release suggested a deficit in GABAergic
transmission in the visual cortex of GAD 65 (/) (Hensch et al.,
1998). To assess the status of GABAergic transmission more directly, we
studied evoked IPSCs under whole-cell voltage-clamp conditions.
Monosynaptic IPSCs were recorded at 0 mV and in the presence of 10 µM CNQX and 100 µM APV to block fast
glutamatergic transmission. We first measured the magnitude of the
maximal IPSC, which provides a mean of comparing the total GABAergic
inputs converging into pyramidal cells (Ling and Benardo, 1999).
Previously, we reported that BDNF-overexpressing mice, which exhibit an
early developmental increase in GAD 65 puncta, also show an accelerated
developmental increase in the maximal IPSC (Huang et al., 1999). Thus,
we expected a reduced maximal IPSC in the GAD 65 (/) mice. Figure
1 summarizes the results. To our
surprise, but in line with a previous study in CA1 (Tian et al., 1999),
we found no significant difference (p = 0.28) in
the magnitude of the maximal IPSCs between GAD 65 (/) (529 ± 33 pA; n = 11) and their age-matched wild-type
littermates (561 ± 25 pA; n = 11). These results
suggest that total GABAergic input converging onto pyramidal cells is
not affected by the deletion of the GAD 65 gene.
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Figure 1.
Normal number of inhibitory inputs in GAD 65 KO
mice. A, Stimulation in layer IV effectively recruits
the maximal IPSCs in layer II/III cells. Diagram on the
left depicts stimulation-recording configuration.
Traces are examples of maximal responses evoked by layer
IV stimulation (1), lateral stimulation
(2), and layer IV and lateral stimulation
together (1 + 2). B,
C, Similar relationship between stimulus intensity and
IPSC magnitude in GAD 65 KO mice and their wild-type
(WT) littermates. A, Example IPSCs
evoked by a series of stimulus of increasing intensity (5, 10, 20, 40, 80, and 160 mA) recorded in layer II/III pyramidal cells from wild type
(left) and an age-matched GAD 65 KO littermate
(right). B, Relationship between IPSC magnitude and
stimulus intensity for wild type (open circles; 11 cells, 6 mice) and GAD 65 KO littermates (filled
circles; 11 cells, 6 mice). Indicated on the
right are the maximal IPSC amplitudes (obtained at 160 mA) for all individual experiments.
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Reduced efficacy of GABAergic synaptic transmission during
repetitive activation in GAD 65
In cortex, inhibitory synaptic transmission is greatly attenuated
during repetitive activation, likely attributable to the progressive depletion of the releasable pool of vesicles (Galarreta and
Hestrin, 1998; Varela et al., 1999). GAD 65, which is specifically localized in the axon terminals, is likely an important factor determining the size of the releasable pool and/or its replenishment after depletion (Tian et al., 1999). In fact, GABAergic transmission during tetanic stimulation is impaired in the CA1 region of the hippocampus of GAD 65 KOs (Tian et al., 1999). The results
shown in Figure 2A
confirmed that this is also the case in visual cortex. In these
experiments, the stimulation intensity was adjusted to evoke IPSCs of
similar amplitude in cells from GAD 65 KO (198 ± 5 pA;
n = 8) and wild-type (202 ± 8; n = 11) mice. However, the response to a 1 sec 100 Hz stimulus train was
much reduced in the GAD 65 KO cells (total charge, 358 ± 25 pC in
GAD 65; 493 ± 58 pC in wild type; p = 0.001).
Indirect evidence from field potential recordings suggest that, in
cortex, GABAergic transmission might be impaired at even lower
frequencies (Hensch et al., 1998). Therefore, we studied the response
of layer II/III cells to trains of 15 stimulation pulses delivered at
different frequencies (50, 30, and 1 Hz). Because prolonged
depolarization can affect the evoked IPSC (Alger and Pitler, 1995),
these experiments were performed at 70 mV rather than at 0 mV. To
allow the measurement of IPSCs at 70 mV, the reversal potential of
Cl was shifted to a more positive value
by increasing the [Cl] in the
recording pipette (see Materials and Methods). As shown in Figure
2B-D, during the train stimulation, the
response magnitude rapidly decreased until it reached a steady level
that depended on the stimulation frequency. The degree of depression at
the steady state was consistently larger in the GAD 65 (/) at all the frequencies tested. A statistical analysis revealed that the differences in frequency-dependent depression between GAD 65 (/) and wild types were highly significant (two-factor ANOVA;
F(1,59) = 15.66; p = 0.0002). These results indicate that the ablation of GAD 65 reduces the
efficacy of inhibitory transmission during prolonged activation.
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Figure 2.
Reduced efficacy of GABAergic synaptic
transmission during repetitive activation in GAD 65 KO mice.
A, Reduced response to tetanic stimulation (100 pulses
at 1 Hz) in cells from GAD 65 KO mice. Superimposed
traces represent the average of the responses of eight cells
from GAD 65 KO mice (thick trace) and 11 cells from
age-matched wild-type (WT) littermate
(thin trace) mice. Stimulation intensity was adjusted to
evoke single IPSCs of similar amplitude in both genotypes. The
inset shows the same average responses at higher
temporal resolution. The total charge flow during the tetanus is shown
on the right bar graph. The response of cell was
integrated and then averaged across genotypes. B,
Examples of responses evoked by 15 pulse trains delivered at 30 Hz
(top) and 50 Hz (bottom) in cells from a
GAD 65 KO (thick trace) mouse and its age-matched
wild-type littermate (thin trace). The
traces (averages of 4 responses) have been normalized to
the response to the first pulse of the train. C, Average
attenuation of the IPSC amplitude during 15 pulse trains delivered at 1 Hz (triangles), 30 Hz (circles), and 50 Hz (squares). Results from wild type are shown on the
left, and results from GAD 65 KOs are on the
right. The curves are single exponentials that give the
best fit to the data. D, Relative amplitudes of IPSC at
steady state (average of the last 3 responses of a train) across
different stimulation frequencies. Open symbols, Wild
type; filled symbols, GAD 65 KO.
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Impaired LTD in visual cortex of GAD 65(/) mice
Experimental evidence indicates that LTD-like mechanisms are
involved in the ocular dominance shifts caused by monocular deprivation in kittens (Rittenhouse et al., 1999). Thus, assessing the status of
LTD in the GAD 65 KO is of obvious relevance for understanding results
obtained with monocular deprivation in these mice. To investigate how
the ablation of GAD 65 affects LTD, we used the standard protocol of
prolonged low-frequency stimulation (LFS) (900 pulses at 1 Hz), which
induces robust LTD in young animals in a number of regions, including
the cortex. For comparative purposes, we also studied LTD in the
Schaffer collateral  CA1 pathway in the hippocampus. All experiments
were done "blind" to the genotype, and Figure
3A summarizes the results. In
the visual cortex, LFS reliably induced LTD in slices from the
wild-type mice (80.1 ± 4.3%; n = 4 mice; 13 slices), but it barely affected the responses recorded in the KO
littermates (97.4 ± 2.7; n = 4 mice; 15 slices).
This difference was highly significant (p < 0.001). In contrast, in CA1, LFS induced comparable levels of LTD
(p = 0.90) in slices from wild-type mice
(77.6 ± 6.1; n = 4 and 9) and their KO
littermates (78.5 ± 3.1; n = 8 and 18). Together,
these results indicate that the ablation of GAD 65 impairs the
induction of LTD specifically in the visual cortex.
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Figure 3.
Induction of LTD with 1 Hz LFS is
impaired in the visual cortex but not in the CA1 region of GAD 65 KO
mice. The graphs depict average changes in the evoked field potentials
induced by LFS (1 Hz, 15 min) in slices of visual cortex
(A) and CA1 (B) prepared
from 3-week-old wild-type (WT) mice (open
circles) and their GAD 65 KO littermates (filled
circles). The LTD magnitude for each individual experiment
(measured 1 hr after LFS) is shown at the right of each
graph. Example field potential traces from experiments performed in
wild-type (top) and KO (bottom) mice are
shown in the right. The superimposed
traces are averages of four consecutive responses recorded 1 min before (thin traces) and 1 hr after (thick
traces) LFS.
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Chronic but not acute application of diazepam restores
cortical LTD in GAD 65 KO mice
The effects of monocular deprivation can be restored
in GAD 65 (/) mice by infusing the benzodiazepine agonist diazepam into the cortex (Hensch et al., 1998). We asked whether this effect of
diazepam was the result of a rescued LTD. It is well established that
GABAergic inhibition regulates the induction of synaptic plasticity by
limiting the activation of NMDA receptors (Artola et al., 1990;
Kirkwood and Bear, 1994). Indeed, manipulations that reduce inhibition
also decrease the magnitude of LTD, whereas manipulations that enhance
inhibition also increase LTD (Steele and Mauk, 1999). Therefore, we
tested whether potentiating the inhibitory response with
benzodiazepines restores LTD in the visual cortex of GAD 65 (/). In
a first series of experiments, diazepam was acutely applied to the
bath. At this concentration (15 µM), diazepam reliably
enhanced the amplitude (170% of control; p = 0.048)
and duration (135% of control; p = 0.027) of the IPSC
recorded in cells from GAD 65(/) mice (n = 5; data
not shown) (Segal and Barker, 1984; Hensch et al., 1998;
Rozas et al., 2001). However, as shown in Figure
4, such bath applications of diazepam
failed to restore LTD in GAD 65 (/), and there was no difference
(p = 0.89) in the magnitude of LTD obtained in
the presence (96.2 ± 3.0; n = 5;15) of the drug
or in interleaved controls (only DMSO, 95.4 ± 3.7;
n = 5;9). Because experience-dependent visual cortex
plasticity was rescued in GAD 65 (/) animals chronically treated
with diazepam (Hensch et al., 1998), we asked whether a prolonged
exposure to diazepam is necessary to restore LTD. In these experiments,
all pups in a given litter were treated with diazepam (10 mg/kg, i.p.,
daily) for 6 d before the experiments. This dosage of diazepam has
been shown previously to reduce excitability and to affect plasticity
(Levkovitz et al., 1999). At the end of the treatment, the
heterozygotes were discarded, and LTD was measured in the GAD 65 (/) and wild-type mice. The experimenter was blind to the genotype
of the animal. As illustrated in Figure 4B, in slices
prepared from diazepam-treated animals, LFS resulted in robust and
comparable (p = 0.91) LTD in both wild type
(84.9 ± 3.4; n = 4 and 11) and GAD 65 (/)
(85.4 ± 2.2; n = 5 and 15). In both cases, the
magnitude of LTD was comparable with the one obtained in slices
prepared from untreated wild-type animals (~80%) (Fig. 1). These
results indicate that chronic but not acute exposure to diazepam is
sufficient to restore LTD in GAD 65 (/) mice.
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Figure 4.
Chronic but not acute application of diazepam
(DZ) restores LTD in the visual cortex of GAD 65 KO
mice. A, LFS does not induce LTD in slices from GAD 65 KO in control conditions (DMSO; open circles) or when 15 µM diazepam was continuously bath applied from 20 min
before experiment (filled circles). B,
Pretreatment with diazepam (10 mg/kg daily; 5-6 d) abolishes the
differences in LTD between wild-type (open circles) and
GAD 65 KO (filled circles) mice. As in Figure 3,
the results from all individual experiments are depicted on the
right of each graph. Representative field potential
traces for each experimental condition are shown on the far
right. The superimposed traces are averages of
four consecutive responses recorded 1 min before (thin
traces) and 1 hr after (thick traces)
LFS.
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DISCUSSION |
Previous studies on GAD 65 (/) mice reported a marked
increase in cortical excitability and a severe reduction in
experience-evoked visual cortical plasticity (Kash et al., 1997; Hensch
et al., 1998). Both outcomes were attributed to the reduced GABAergic function associated with the elimination of GAD 65. We found that, in
addition, at least one mechanism of synaptic modification, LTD, is
impaired in the visual cortex of GAD 65 (/) mice. As discussed
below, such findings bear obvious relevance for understanding the lack
of visual cortical plasticity in GAD 65 (/).
GAD 65, one of the two isoforms of the GABA-synthesizing enzyme GAD,
locates primarily in the axon terminals (Esclapez et al., 1994).
Because of its subcellular location and dependence of cofactors, GAD 65 is believed to be important at times of increased synaptic activity. In
CA1, the genetic deletion of GAD 65 does not affect basal GABAergic
transmission, but it compromises the ability to sustain repetitive
activation. Similarly, in visual cortex, the steady-state response to
prolonged stimulation was clearly reduced in GAD 65 (/). In
contrast, the magnitude of the maximal IPSC, which reflects the number
and potency of GABAergic inputs targeting a cell (Ling and Benardo,
1999), was not affected by the mutation. Thus, the availability of GAD
65 appears to be a limiting factor for the efficacy of transmission at
high frequencies but not the potency or number of GABAergic inputs in
visual cortex.
Besides the expected deficit in inhibitory transmission, the
ablation of GAD 65 (/) also impaired LTD of excitatory transmission in visual cortex. In a previous study, Hensch et al. (1998) reported normal LTD and LTP in the GAD 65 (/) mice. This discrepancy might
be related to the age of the animals used. In mice, unlike most other
species studied, the induction of LTD with 1 Hz LFS is strongly
regulated during development such that, after P30, 1 Hz no longer
induces much LTD, not even in CA1 (Mayford et al., 1995; Kirkwood et
al., 1997) (our unpublished observations). In the study of Hensch et
al. (1998), the animals were older (P24-P33) and showed much less LTD
(10% LTD in wild types) compared with our study (P21-P27; ~20% LTD
in wild types). The smaller magnitude of depression combined with short
preconditioning baselines (only 10 min by Hensch et al., 1998) makes it
difficult to discern whether those changes represent LTD or a drift
in basal responses. In any case, the smaller magnitude of LTD in wild
types would make those measurements unsuitable for detecting a deficit
in LTD.
We showed that LTD could be rescued in GAD 65 (/) mice by
chronically treating the animals with diazepam. However, acute application of diazepam did not restore LTD. These results suggest that
the LTD deficit is not directly attributable to reduced inhibitory tone
per se during 1 Hz conditioning stimulation. An alternative hypothesis
is that the LTD deficit in GAD 65 (/) mice is a consequence of the
history of enhanced cortical activity in vivo. It is also possible that LTD is intact in GAD 65(/) mice, but the mutation affected cortical circuits in such a way that they are not
effectively recruited by 1 Hz conditioning. Whether the increased
activity in GAD 65 (/) mice already induced LTD and saturated it,
or whether it caused the downregulation of the LTD mechanisms or affected the frequency-dependency of its induction, remains to be
investigated. In this respect, it is worth mentioning that, in
dark-reared animals, in which increased spontaneous activity and
cortical excitability suggest a weaker inhibition (Benevento et al.,
1992), the induction of LTD ex vivo is clearly downregulated (Kirkwood et al., 1996). In any case, these results suggest that the
inhibitory tone plays an important role in the regulation of synaptic
plasticity in visual cortex.
In contrast to visual cortex, the induction of LTD was normal in the
CA1 region of GAD 65 (/). It is possible that the alterations in
GABAergic function in GAD 65 (/) are more severe in cortex than in hippocampus. Consistent with that idea, the deficit in GABAergic transmission were revealed by a much milder type of stimulation in cortex (15 pulses at 30 Hz) than in CA1 (100 pulses at
100 Hz by Tian et al., 1999). Alternatively, LTD in cortex might be
more responsive to changes in GABAergic transmission. A clear
example of higher vulnerability of cortical plasticity is provided by
the  -CaM kinase II knock-out heterozygotes, which display selective
deficit of LTP in the cortex but not in CA1(Frankland et al., 2001).
The seemingly labile synaptic plasticity in the cortex might be related
to the fact that its induction is tightly regulated (Kirkwood et al.,
1999; Kojic et al., 2000).
In the original characterization of visual cortical plasticity in GAD
65 (/) mice, the lack of ocular dominance plasticity was attributed
solely to the altered balance of excitation and inhibition. The
possible role of NMDA receptor-dependent synaptic plasticity was
dismissed on the grounds that LTP and LTD were normal in these mice
(Hensch et al., 1998). Our results showing a profound deficit of LTD in
younger animals are consistent with the alternative hypothesis that LTD
is a mechanism for weakening inputs from the deprived eye (Rittenhouse
et al., 1999). According to this view, the lack of LTD in GAD 65 (/) would render these mice refractory to the normal effects of
monocular deprivation. On the other hand, chronic diazepam would be
expected to restore experience-dependent plasticity by rescuing LTD in
these mice.
The importance of GABAergic circuits in visual cortical plasticity is
well established, but their exact role has remained elusive and
controversial at times, perhaps because most interpretations have
focused on the direct inhibitory actions of GABAergic transmission. Our
results indicate that the inhibitory tone might also regulate the
modification of excitatory synapses, revealing an additional level of
complexity in the interaction between excitatory and inhibitory circuits.
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FOOTNOTES |
Received Dec. 18, 2001; revised March 15, 2002; accepted April 4, 2002.
*
S.-Y.C. and B.M. contributed equally to this work.
This study was supported by National Institutes of Health Grants
R01-EY12124-03 and P50-MH58880-01. We thank Dr. Mark Bear for valuable
comments on this manuscript and Dr. Jokubas Zirbukus for technical help.
Correspondence should be addressed to Alfredo Kirkwood, Mind Brain
Institute, Johns Hopkins University, 338 Krieger Hall, 3400 North
Charles Street, Baltimore, MD 21218. E-mail: kirkwood{at}jhu.edu.
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REFERENCES |
-
Aizenman C,
Kirkwood A,
Bear M
(1996)
Current source density analysis of evoked responses in visual cortex in vitro: implications for the regulation of long-term potentiation.
Cereb Cortex
6:751-758[Abstract/Free Full Text].
-
Alger BE,
Pitler TA
(1995)
Retrograde signaling at GABAA-receptor synapses in the mammalian CNS.
Trends Neurosci
18:333-340[ISI][Medline].
-
Artola A,
Brocher S,
Singer W
(1990)
Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex.
Nature
347:69-72[Medline].
-
Benevento LA,
Bakkum BW,
Port JD,
Cohen RS
(1992)
The effects of dark rearing on the electrophysiology of the rat visual cortex.
Brain Res
572:198-207[ISI][Medline].
-
Blue ME,
Parnavelas JG
(1983)
The formation and maturation of synapses in the visual cortex of the rat. II. Quantitative analysis.
J Neurocytol
12:697-712[ISI][Medline].
-
Daw N,
Gordon B,
Fox K,
Flavin H,
Kirsch J,
Beaver C,
Ji Q,
Reid S,
Czepita D
(1999)
Injection of MK-801 affects ocular dominance shifts more than visual activity.
J Neurophysiol
81:204-215[Abstract/Free Full Text].
-
Di Cristo G,
Berardi N,
Cancedda L,
Pizzorusso T,
Putignano E,
Ratto GM,
Maffei L
(2001)
Requirement of ERK activation for visual cortical plasticity.
Science
292:2337-2340[Abstract/Free Full Text].
-
Esclapez M,
Tillakaratne NJ,
Kaufman DL,
Tobin AJ,
Houser CR
(1994)
Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms.
J Neurosci
14:1834-1855[Abstract].
-
Fagiolini M,
Pizzorusso T,
Berardi N,
Domenici L,
Maffei L
(1994)
Functional postnatal development of the rat primary visual cortex and the role of visual experience: dark rearing and monocular deprivation.
Vision Res
34:709-720[ISI][Medline].
-
Frankland PW,
O'Brien C,
Ohno M,
Kirkwood A,
Silva AJ
(2001)
Alpha-CaMKII-dependent plasticity in the cortex is required for permanent memory.
Nature
309:309-313.
-
Galarreta M,
Hestrin S
(1998)
Frequency-dependent synaptic depression and the balance of excitation and inhibition in the neocortex.
Nat Neurosci
1:539-541[ISI][Medline].
-
Gordon JA,
Cioffi D,
Silva AJ,
Stryker MP
(1996)
Deficient plasticity in the primary visual cortex of -calcium/calmodulin-dependent protein kinase II mutant mice.
Neuron
17:491-499[ISI][Medline].
-
Guo Y,
Kaplan IV,
Cooper NG,
Mower G
(1997)
Expression of two forms of glutamic acid decarboxylase (GAD67 and GAD65) during postnatal development of the cat visual cortex.
Brain Res Dev Brain Res
103:127-141[Medline].
-
Hensch TK,
Faglioni M,
Mataga N,
Stryker MP,
Baekkeskov S,
Kash SF
(1998)
Local GABA circuit control of experience-dependent plasticity in developing visual cortex.
Science
282:1504-1508[Abstract/Free Full Text].
-
Huang JZ,
Kirkwood A,
Pizzorusso T,
Porciatti V,
Morales B,
Bear MF,
Maffei L,
Tonegawa S
(1999)
BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex.
Cell
98:739-755[ISI][Medline].
-
Hubel DH,
Wiesel TN
(1970)
The period of susceptibility to the physiological effects of unilateral eye closure in kittens.
J Physiol (Lond)
206:419-436[Abstract/Free Full Text].
-
Kash SF,
Johnson RS,
Tecott LH,
Noebels JL,
Mayfield RD,
Hanahan D,
Baekkeskov S
(1997)
Epilepsy in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase.
Proc Natl Acad Sci USA
94:14060-14065[Abstract/Free Full Text].
-
Kirkwood A,
Bear MF
(1994)
Hebbian synapses in visual cortex.
J Neurosci
14:1634-1645[Abstract].
-
Kirkwood A,
Rioult MG,
Bear MF
(1996)
Experience-dependent modification of synaptic plasticity in visual cortex.
Nature
381:526-528[Medline].
-
Kirkwood A,
Silva A,
Bear MF
(1997)
Age-dependent decrease of synaptic plasticity in the neocortex of alphaCaMKII mutant mice.
Proc Natl Acad Sci USA
94:3380-3383[Abstract/Free Full Text].
-
Kirkwood A,
Rozas C,
Kirkwood J,
Perez F,
Bear MF
(1999)
Modulation of long-term depression in visual cortex by acetylcholine and norepinephrine.
J Neurosci
19:1599-1609[Abstract/Free Full Text].
-
Kojic L,
Dyck RH,
Gu Q,
Douglas RM,
Matsuraba J,
Cynader MS
(2000)
Columnar distribution of serotonin-dependent plasticity within kitten striate cortex.
Proc Natl Acad Sci USA
97:1841-1844[Abstract/Free Full Text].
-
Komatsu Y
(1983)
Development of cortical inhibition in kitten striate cortex investigated by a slice preparation.
Dev Brain Res
8:136-139.
-
Levkovitz Y,
Avignone E,
Groner Y,
Segal M
(1999)
Upregulation of GABA neurotransmission suppresses hippocampal excitability and prevents long-term potentiation in transgenic superoxide dismutase-overexpressing mice.
J Neurosci
19:10977-10984[Abstract/Free Full Text].
-
Ling DS,
Benardo L
(1999)
Restrictions on inhibitory circuits contribute to limited recruitment of fast inhibition in rat neocortical pyramidal cells.
J Neurophysiol
82:1793-1807[Abstract/Free Full Text].
-
Luhmann HJ,
Prince DA
(1991)
Postnatal maturation of the GABAergic system in rat neocortex.
J Neurophysiol
65:247-263[Abstract/Free Full Text].
-
Mayford M,
Wang J,
Kandel E,
O'Dell T
(1995)
CaMKII regulates the frequency-response function of hippocampal synapses for the production of both LTD and LTP.
Cell
81:1-20[ISI][Medline].
-
Rittenhouse CD,
Shouval HZ,
Paradiso MA,
Bear MF
(1999)
Monocular deprivation induces homosynaptic long-term depression in visual cortex.
Nature
397:347-350[Medline].
-
(2001) Developmental inhibitory gate controls the
relay of activity to the superficial layers of the visual cortex.
J Neurosci 21:6791-6801.
-
Segal M,
Barker JL
(1984)
Rat hippocampal neurons in culture: voltage-clamp analysis of inhibitory synaptic connections.
J Neurophysiol
52:469-487[Abstract/Free Full Text].
-
Singer W
(1995)
Development and plasticity of cortical processing architectures.
Science
270:758-759[Abstract/Free Full Text].
-
Steele PM,
Mauk MD
(1999)
Inhibitory control of LTP and LTD: stability of synapse strength.
J Neurophysiol
81:1559-1566[Abstract/Free Full Text].
-
Tian N,
Petersen C,
Kash S,
Baekkeskov S,
Copenhagen D,
Nicoll R
(1999)
The role of the synthetic enzyme GAD65 in the control of neuronal gamma-aminobutyric acid release.
Proc Natl Acad Sci USA
96:12911-12916[Abstract/Free Full Text].
-
Varela JA,
Song S,
Turrigiano GG,
Nelson SB
(1999)
Differential depression at excitatory and inhibitory synapses in visual cortex.
J Neurosci
19:4293-4304[Abstract/Free Full Text].
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